Our preliminary experiments have shown that rat donor histocompatability (HC) antigens covalently coupled to recipient spleen cells can be used to induce antibody tolerance to allogeneic cells. Detergent-solubilized HC antigens will be coupled to tolerogenic carrier cells with a carbodiimide reagent and used to study transplantation tolerance in two rat heterotopic cardiac allograft models. Experiments are designd to study the kinetics of humoral and cellular tolerance with HC antigen-cell conjugates, to improve the conjugation technique, to investigate the mechanism of tolerance and to extend the observations to other strains and species. Affinity chromatography, immunofluorescence, radio-labeling, microsurgical transplantation, mixed lymphocyte culture, cell fractionation and transfer techniques will be used.